Activation of proliferation of corneal endothelium with a solution "gekomen"

 

(57) Abstract:

The invention relates to ophthalmology. The method includes the introduction of the solution "Gekomen" of the following composition: heparin 5-100 units; glycosaminoglycans of 0.01-0.5 mg; complex glycosaminoglycan-copper 0.005 to 0.15 mg in 1 ml of balanced salt solution. The method can reduce the loss of endothelium in the postoperative period, and at keratopathy and initial endothelial-epithelial dystrophy reduce corneal edema, increase the density of the endothelium. 5 C.p. f-crystals.

The invention relates to the field of medicine and more specifically to ophthalmology.

It is known that the possibility of mitotic division in the endothelium of the cornea of a person is very limited. Regeneration of the endothelium, as a rule, is the result of hypertrophy and expansion of endothelial cells and their migration. By reducing the density of endothelial cells in the result of accidental injury or operating, or diseases of the eye below the critical level (less than 1000 cells/mm2), can develop endothelial-epithelial corneal dystrophy.

There is a method of activation of proliferation of corneal endothelium with a solution containing heparin, copper ions and SBM phosphate buffer at a pH of 7.4 (U.S. Pat. RF N2077878 from 30.06.93). Such a solution has a stimulating effect on the activity of the endothelium, however, when using such a solution in a small percentage of cases, there was the emergence of givemy due to the unbalanced number of heparin, which reduces the effectiveness.

The objective of the invention is to provide a safe and effective method of activation of proliferation of corneal endothelium to prevent decrease of the density of the endothelium during surgery, as well as restoration of damaged corneal endothelium person in postoperative keratopathy and the development of secondary endothelial-epithelial dystrophy.

The technical result of the invention is to reduce the loss of endothelium in the postoperative period, and at postoperative keratopathy and initial secondary endothelial - epithelial dystrophy of swelling of the cornea, increasing the density of the endothelium and the disappearance of the discomfort of the patient.

The technical result is achieved in that in the method of activation of proliferation of corneal endothelium, including the introduction of heparin solution in a balanced salt solution into the anterior segment of ego composition:

Heparin - 5-100 units

Glycosaminoglycans of 0.01-0.5 mg

Complex glycosaminoglycan-copper - 0.005 to 0.15 mg

in 1 ml of balanced salt solution, as a balanced salt solution using a solution with a pH of 7.2 and 7.6 in the following ratio, wt.%:

Sodium chloride - 0,85 - 0,95

One-deputizing sodium phosphate - 0,0025 - 0,0040

Disubstituted phosphate sodium - 0,0115-0,0135

Purified water - the Rest

One of the variants of the invention lies in the fact that when cataract extraction with implantation of an intraocular lens (IOL) or refractive IOL implantation with the aim of activating solution fills the anterior chamber of the eye after surgery, or provide irrigation during the whole operation activating solution in the amount of 50 to 200 ml.

To reduce the loss of the density of endothelial cells after surgery activating solution is injected subkonyunktivalno of 0.3 ml daily for 3 days.

In the postoperative period when keratopathy, or in the development of the initial stage of the secondary endothelial-epithelial dystrophy activating solution is injected subkonyunktivalno 0.3 ml daily for 5 to 10 days, or metopolitan 5 ml daily in doing so, a 5-8 sessions.

Activating solution may optionally contain viscoelastic in the amount of 90 to 99 wt.% and they fill the anterior chamber of the eye at the initial stage of the operation.

Heparin and glycosaminoglycans are natural polysaccharides built from repeating disaccharide glycosides of components, which usually contain amino sugar and uronic acid. Addition of heparin to glycosaminoglycans include Kermanshah, chondroitin sulfate, hyaluronic acid, heparansulfate, dermatologit. All glycosaminoglycans (GAGS) are polyanionic due to the presence in their structure of acidic sulfate groups or carboxyl groups of uronic acids. With this feature GAGS involve many functional properties. GAG are integral components of connective tissue. They are actively involved in water-salt metabolism, can reduce inflammatory and exudative reaction with injuries, stimulate the repair of damaged corneal tissue and primarily endothelium and keratocytes.

Heparin in addition to these properties has a specific action - it activates fibroblast growth factor from descemets membrane horn obookiah, relevant physiological (osmotolerant and a pH of tissue fluid), contains copper ions, which increase the mobility of the cells is a necessary part of the process of regeneration.

Boundary concentrations of the components of the activating solution was determined experimentally. The concentration of heparin was expressed in units of anticoagulant activity, because the allocation of heparin from different sources one weight unit corresponds to a different anticoagulant activity. So the same units of heparin may have different anticoagulant activity, including that which leads to bleeding. This can lead to complications when using an activating solution. Heparin concentration 5 u/ml is the minimum required for the activation of fibroblast growth factor, and at concentrations higher heparin 100 IU/ml observed increased bleeding.

When the concentration of GAG below 0.01 mg/ml were not observed in the amplification of proliferation of corneal endothelium of the rabbit in the dosed area of injury. When the concentration of GAG than 0.5 mg/ml was observed reduced proliferation keratocytes corneal stroma electron-microscopically.Leah cornea of the rabbit in the dosed area of the defect. When the concentration of the complex GAG-copper above 0.15 mg/ml was observed inhibition of endothelium, and when the concentration of the complex GAG-copper below 0.005 mg/ml did not accelerate the recovery of the endothelium.

The viscoelastics is viscous solutions of various substance used in ophthalmic surgery to maintain the volume of the anterior chamber and the mechanical protection of the corneal endothelium from injury during surgery. They are entered in the anterior chamber of the eye at the initial stage of the operation and displayed on the final stage. Currently used in surgical practice solutions derived methylcellulose - Occucoat (Eye of the World, v.2, N3, p.62, 1997), Vision (U.S. Pat. RF N 2114587), of sodium hyaluronate - Provisc, Healon (J. Cataract Refract Surg. , 1998, 24, 1130 - 1135), chondroitin sulphate sodium - Viscoat (J. Cataract Refract Surg., 1998, 24, 678 - 683).

The solution for stimulating the proliferation of corneal endothelium obtained as follows. First, obtain a series of GAGS with copper ions (GAG-copper). To do this, to a solution of GAG concentration from 0.5 to 2.0 mg/ml in 0.1 M Tris-HCl buffer pH 7,4 add the copper sulfate in a five-fold excess by weight, mix and leave at 4 to 8oC on the day. Complex GAG-copper allocate using gel chromatography, freed from low molecular weight impurities. Konz is onetimeteardown blue (Connective Tissue Research. , 1982, v.9, p. 247-248.). Then make a mixture of components activating solution in concentrations according to the claims.

The method is as follows.

For surgical interventions, accompanied by the opening of the anterior chamber of the eye, such as cataract extraction or implantation of the IOL, and so on, activating solution "Gekomen" fill the anterior chamber at the final stage of the operation so that he had a direct contact with the corneal endothelium in the first postoperative hours, gradually being replaced by Sekretareva chamber moisture patient. Under similar operational interventions activating solution may be irrigation of the anterior chamber during the entire period of the operation.

When performing the same surgical interventions activating solution "Gekomen", optionally containing viscoelastic, fill in front of the camera instead of the traditionally used viscoelastics at the initial stage of the operation. At the final stage of the operation specified by an activating solution is aspirated from the anterior chamber.

To reduce the loss of endothelial cells in the early postoperative period after cataract extraction, and is erali daily for 3 days 0.3 ml.

In cases of postoperative keratopathy or initial stage endothelial-epithelial dystrophy of the cornea activating solution "Gekomen" enter subkonyunktivalno daily for 5-10 days to 0.3 ml In similar cases activating solution "Gekomen" can be entered by phonophoresis. With this purpose, placed 5 ml of solution in foretical bath, placed on the cornea, and spend phonophoresis in continuous mode for 10 minutes at the intensity of 0.2-0.3 W/cm2. Phonophoresis spend daily for 5-8 days.

Examples.

Example 1. Patient M., 53 L., diagnosed with immature complicated cataract of the right eye. The density of endothelial cells (PEC) 2500-2600 cells/mm2. Performed phacoemulsification with IOL implantation. Upon completion of the operation in the anterior chamber was entered 0.3 ml activating solution "Gekomen" of the following composition: heparin 100 units , GAG 0.01 mg, complex GAG-copper 0.005 mg in 1 ml of balanced salt solution. At 1 month after surgery PEK 2300-2500 cells/mm26 months PEK 2300-2500 cells/mm2. Loss PEK amounted to 5.9%, while the average loss PEK when performing similar operations without the use of Glucomen" is 10.6%.

26 months 2500-2700 cells/mm2. Loss peck was 7.1%, while the average loss PEK with similar operations without the use of Glucomen" is 13.7%.

Example 3. Patient G. , 70 HP, the diagnosis of Mature senile cataract of the left eye, PEK 2500-2700 cells/mm2. Performed extracapsular cataract extraction with IOL implantation. Upon completion of the operation subkonyunktivalno were administered 0.3 ml of Glucomen" daily for 3 days following composition: 5 units of heparin, GAG 0.2 mg, complex GAG-copper 0.15 mg in 1 ml of balanced salt solution. At 1 month after surgery PEK 2500-2600 cells/mm26 months PEK 2400-2600 cells/mm2. Loss peck was 3.8%, while the average loss PEK with similar operations without the use of Glucomen" is 12.5%.

Example 4. Patientchoice of the cornea in the Central optical zone 607 μm. A course of conservative treatment, including daily phonophoresis of the cornea for 5 days using an activating solution "Gekomen" of the following composition: 5 units of heparin , GAG 0.5 mg, complex GAG-copper 0.15 mg in 1 ml of balanced salt solution. To conduct phonophoresis in foretical bath was placed 5 ml of Glucomen" specified structure and held phonophoresis in continuous mode for 10 minutes at the intensity of 0.2-0.3 W/cm2. After 1 month of treatment PEK 1000-1100 cells/mm2through 3 months after treatment 800-1000. Conducted refresher course phonophoresis, then PEK increased from 900 to 1000 cells/mm2and continued to remain stable for 1 year. The thickness of the cornea in the Central optical zone of the cornea after treatment decreased to 534 ám.

Example 5. Patient P., 72 HP, the diagnosis of Mature brown cataract of the right eye, PEK 1900-2100 cells/mm2. Performed extracapsular cataract extraction with IOL implantation. As the activating solution used "Gekomen", optionally containing viscoelastic, of the following composition: heparin 100 units, GAG 0.01 mg, complex GAG-copper 0.15 mg, viscoelastic 0,99 g in 1 ml of balanced salt solution. After 1 month operas is losing PEK with similar operations without the use of "Gekomen" is 11.6%.

1. Activation of proliferation of corneal endothelium, including the introduction of heparin solution in a balanced salt solution into the anterior segment of the eye, characterized in that the activating solution further contains glycosaminoglycans and complex glycosaminoglycans with copper ions in the following ratio of components in 1 ml of balanced salt solution:

Heparin - 5 - 100%

Glycosaminoglycans of 0.01 - 0.5 mg

Complex glycosaminoglycan - copper - 0.005 to 0.15 mg

2. The method according to p. 1, characterized in that as a balanced salt solution using a solution with a pH of 7.2 and 7.6 in the following ratio, wt.%:

Sodium chloride - 0,85 - 0,95

One-deputizing sodium phosphate - 0,0025 - 0,0040

Disubstituted phosphate sodium - 0,0115 - 0,0135

Purified water - the Rest

3. The method according to p. 1 - 2, characterized in that during cataract extraction with IOL implantation or after implantation of IOL refractive objective activating solution fills the anterior chamber of the eye at the end of the operation or conduct irrigation activating solution for all operations in the amount of 50 to 200 ml.

4. The method according to PP.1 and 2, characterized in that to reduce the loss lechenie 3 days.

5. The method according to PP.1 and 2, characterized in that in the postoperative period when keratopathy or during the development of the initial stage of the secondary endothelial-epithelial dystrophy activating solution is injected subkonyunktivalno 0.3 ml daily for 5 to 10 days, or method phonophoresis through the cornea in a continuous mode for 10 minutes, when the intensity of 0.2 - 0.3 W/cm2using 5 ml daily, in doing so, a 5 - 8 sessions.

6. The method according to p. 1, characterized in that the activating solution, optionally containing viscoelastic in the amount of 90 to 99 wt.%, fill the anterior chamber at the initial stage of cataract extraction.

 

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3 cl, 5 dwg

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